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Genome-wide analysis of histone modifications and gene expression during decidualization in human endometrial stromal cells.

Research Project

Project/Area Number 25293343
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionYamaguchi University

Principal Investigator

SUGINO Norihiro  山口大学, 医学(系)研究科(研究院), 教授 (10263782)

Co-Investigator(Kenkyū-buntansha) YAMAGATA Yoshiaki  山口大学, 医学部附属病院, 准教授 (30363120)
Co-Investigator(Renkei-kenkyūsha) SUYAMA Mikita  九州大学, 生体防御医学研究所, 教授 (70452365)
OOKAWA Yasuyuki  九州大学, 医学研究院, 准教授 (80448430)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords子宮内膜 / 脱落膜化 / エピジェネティクス / ヒストン修飾 / 転写調節 / 次世代シークエンサー
Outline of Final Research Achievements

Dramatic changes of gene expressions occur in human endometrial stromal cells (ESC) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by histone modifications. Here, we investigated genome-wide changes in histone modifications associated with decidualization in human ESC using next-generation sequencing. ESC were incubated with estradiol and medroxyprogesterone acetate to induce decidualization. Decidualization increased H3K27ac and H3K4me3 signals in many genomic regions. RNA-sequence showed that decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with the insulin signaling, which is involved in glucose uptake that is necessary for ESC to undergo decidualization.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 11 results,  Acknowledgement Compliant: 6 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results)

  • [Journal Article] Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation.2016

    • Author(s)
      Maekawa R, Lee L, Okada M, Asada H, Shinagawa M, Tamura I, Sato S, Tamura H, Yamamoto S, Sugino N
    • Journal Title

      Journal of Ovarian Research

      Volume: 9 Pages: 15-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis.2016

    • Author(s)
      Urahama T, Harada A, Maehara K, Horikoshi N, Sato K, Sato Y, Shiraishi K, Sugino N, Osakabe A, Tachiwana H, Kagawa W, Kimura H, Ohkawa Y, Kurumizaka H
    • Journal Title

      Epigenetics & Chromatin

      Volume: 9 Pages: 2-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR.2016

    • Author(s)
      Maekawa R, Sato S, Okada M, Lee L, Tamura I, Jozaki K, Kajimura T, Asada H, Yamagata Y, Tamura H, Yamamoto S, Sugino N
    • Journal Title

      Molecular Endocrinology

      Volume: 30 Pages: 335-347

    • NAID

      130007024986

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Retinoic acid has the potential to suppress endometriosis development.2015

    • Author(s)
      Yamagata Y, Takaki E, Shinagawa M, Okada M, Jozaki K, Lee L, Sato S, Maekawa R, Taketani T, Asada H, Tamura H, Nakai A, Sugino N
    • Journal Title

      Journal of Ovarian Research

      Volume: 8 Pages: 49-49

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Putative epimutagen in maternal peripheral and cord blood samples identified using human induced pluripotent stem cells.2015

    • Author(s)
      Arai Y, Hayakawaa K, Arai D, Ito R, Iwasaki Y, Saito K, Akutsu K, Takatori S, Ishii R, Hayashi R, Izumi S, Sugino N, Kondo F, Horie M, Nakazawa H, Makino T, Hirosawa M, Shiota K, Ohgane J
    • Journal Title

      BioMed Research International

      Volume: 2015 Pages: 1-13

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Melatonin protects the integrity of granulosa cells by reducing oxidative stress in nuclei, mitochondria, and plasma membranes in mice.2015

    • Author(s)
      Tanabe M, Tamura H, Taketani T, Okada M, Lee L, Tamura I, Maekawa R, Aasada H, Yamagata Y, Sugino N
    • Journal Title

      Journal of Reproduction and Development

      Volume: 61 Pages: 35-41

    • NAID

      130004703737

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genome-wide analysis of histone modifications in human endometrial stromal cells.2014

    • Author(s)
      Tamura I, Ohkawa Y, Sato T, Suyama M, Jozaki K, Okada M, Lee L, Maekawa R, Asada H, Sato S, Yamagata Y, Tamura H, Sugino N
    • Journal Title

      Molecular Endocrinology

      Volume: 28 Pages: 1656-1669

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide DNA methylation profiling in cultured eutopic and ectopic endometrial stromal cells.2014

    • Author(s)
      Yamagata Y, Nishino K, Takaki E, Sato S, Maekawa R, Nakai A, Sugino N
    • Journal Title

      PLOS ONE

      Volume: 9(1)

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of C/EBPB binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL and Mn-SOD by cAMP2014

    • Author(s)
      Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, Asada H, Yamagata Y, Tamura H, Sugino N
    • Journal Title

      Endocrinology

      Volume: 155 Pages: 275-286

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanism of luteinization.2014

    • Author(s)
      Sugino N
    • Journal Title

      Obstetrics & Gynecology Science

      Volume: 57 Pages: 93-101

    • NAID

      110009586174

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential mechanisms of aberrant DNA hypomethylation on the X chromosome in uterine leiomyomas.2014

    • Author(s)
      Sato S, Maekawa R, Yamagata Y, Asada H, Tamura I, Lee L, Okada M, Tamura H, Sugino N
    • Journal Title

      Journal of Reproduction and Development

      Volume: 60 Pages: 47-54

    • NAID

      130003381861

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Importance of C/EBPB binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL and Mn-SOD by cAMP in human endometrial stromal cells.2014

    • Author(s)
      Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, Asada H, Yamagata Y, Tamura H, Sugino N
    • Journal Title

      Endocrinology

      Volume: 155 Pages: 275-286

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in female rats.2013

    • Author(s)
      Lee L, Asada H, Kizuka F, Tamura I, Maekawa R, Taketani T, Sato S, Yamagata Y, Tamura H, Sugino N
    • Journal Title

      Endocrinology

      Volume: 154 Pages: 458-470

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 教育講演:黄体化の分子メカニズム2016

    • Author(s)
      杉野 法広
    • Organizer
      第20回日本生殖内分泌学会
    • Place of Presentation
      神戸市,(神戸国際会議場)
    • Year and Date
      2016-01-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR (tissue-dependent and differentially methylated region).2015

    • Author(s)
      Asada H, Okada M, Tamura H, Sugino N
    • Organizer
      The 71th Annual meeting of the American Society of Reproductive Medicine 2015
    • Place of Presentation
      Baltimore, USA
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特別講演:子宮内膜脱落膜化とエピジェネティクス2015

    • Author(s)
      杉野 法広
    • Organizer
      第132回近畿産科婦人科学会学術集会
    • Place of Presentation
      神戸市,(神戸国際会議場)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR (tissue-dependent and differentially methylated region).2015

    • Author(s)
      Maekawa R, Okada M, Tamura H, Sugino N.
    • Organizer
      48th Annual Meeting of the Society for the Study on Reproduction
    • Place of Presentation
      Puerto Rico, USA
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シンポジウム:着床に伴う脱落膜化とその分子機構2015

    • Author(s)
      杉野法広
    • Organizer
      第60回日本生殖医学会
    • Place of Presentation
      横浜市,(パシフィコ横浜)
    • Year and Date
      2015-04-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Epigenome-transcriptome-interactome approach facilitates the investigation of undelying epigenetical deregulation in uterine leiomyomas.2015

    • Author(s)
      Maekawa R, Sato S, Jozaki K, Okada M, Shinagawa M, Lee L, Asada H, Taketani T, Yamagata Y, Tamura H, Sugino N.
    • Organizer
      IFFS (International Federation of Fertility Society)/JSRM (Japan Society for Reproductive Medicine) International Meeting 2015
    • Place of Presentation
      Yokohama, (パシフィコ横浜)
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genome-wide analysis of histone modifications in human endometrial stromal cells undergoing decidualization by next-generation sequencing.2015

    • Author(s)
      Jozaki K, Okada M, Maekawa R, Tamura H, Sugino N.
    • Organizer
      IFFS (International Federation of Fertility Society)/JSRM (Japan Society for Reproductive Medicine) International Meeting 2015
    • Place of Presentation
      Yokohama, (パシフィコ横浜)
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生涯研修プログラム:プロゲステロン産生調節2015

    • Author(s)
      杉野法広
    • Organizer
      日本産科婦人科学会学術集会
    • Place of Presentation
      横浜市,(パシフィコ横浜)
    • Year and Date
      2015-04-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 黄体機能の基礎知識-不妊治療への示唆-2014

    • Author(s)
      杉野法広
    • Organizer
      日本生殖医学会学術講演会
    • Place of Presentation
      東京都,新宿区(京王プラザホテル)
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 子宮内膜の発育とその異常2014

    • Author(s)
      杉野法広
    • Organizer
      日本産婦人科医会学術集会
    • Place of Presentation
      香川県高松市,(JRホテルクレメント高松)
    • Year and Date
      2014-10-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Epigenome-interactome approach facilities the investigation of underlying epigenetical deregulation in uterine leiomyomas.2014

    • Author(s)
      R. Maekawa , I. Tamura , N. Sugino
    • Organizer
      47th Annual Meeting of the Society for the Study on Reproduction
    • Place of Presentation
      Grand Rapids, USA
    • Year and Date
      2014-07-18 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genome-wide analysis of histone modifications associated with decidualization in human endometrial stromal cells.2014

    • Author(s)
      I. Tamura , R. Maekawa , N. Sugino
    • Organizer
      47th Annual Meeting of the Society for the Study on Reproduction
    • Place of Presentation
      Grand Rapids, USA
    • Year and Date
      2014-07-18 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Induction of IGFBP-1, PRL and Mn-SOD by cAMP is associated with histone acetylation status of their promoters in human endometrial stromal cells.2014

    • Author(s)
      H. Asada, M Okada, H. Tamura, N.Sugino
    • Organizer
      The 30th Annual Meeting of the European Society of Human Reproduction and Embryology
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2014-06-28 – 2014-07-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Induction of IGFBP-1, PRL, and Mn-SOD by cAMP is associated with histone acetylation status of C/EBP b binding site of their promoters in human endometrial stromal cells.2014

    • Author(s)
      N. Sugino, I. Tamura
    • Organizer
      61st Annual meeting of Society for Gynecologic Investigation
    • Place of Presentation
      Florence, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] Induction of IGFBP-1 and PRL by cAM is associated with histone acetylation in the promoter region in human endometrial stromal cells.2013

    • Author(s)
      I. Tamura, N. Sugino
    • Organizer
      Society for Reproductive Medicine
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechamisms of luteinization.

    • Author(s)
      N. Sugino
    • Organizer
      The 13th Korea-Japan Joint Conference of Obstetrics and Gynecology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-21   Modified: 2020-04-17  

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